中华医学杂志
中華醫學雜誌
중화의학잡지
National Medical Journal of China
2015年
22期
1731-1735
,共5页
金志贤%王清%毕虹%周开华%何乐伟%和煦%吴琦%潘兴华
金誌賢%王清%畢虹%週開華%何樂偉%和煦%吳琦%潘興華
금지현%왕청%필홍%주개화%하악위%화후%오기%반흥화
肺气肿%间质干细胞移植%治疗效果%大鼠
肺氣腫%間質榦細胞移植%治療效果%大鼠
폐기종%간질간세포이식%치료효과%대서
Pulmonary emphysema%Mesenchymal stem cell transplantation%Treatment outcome%Rats
目的 探讨骨髓来源间充质干细胞(MSCs)移植对大鼠肺气肿的疗效及其可能机制.方法 24只雌性SD大鼠按随机数字表法随机分为对照组、肺气肿组、MSCs移植组各8只,将肺气肿组与MSCs移植组大鼠烟雾暴露14周,制作肺气肿大鼠模型,予MSCs移植组大鼠通过尾静脉输注6-二乙酰基-2-苯基吲哚(DAPI)标记的骨髓来源MSCs.MSCs移植后第14、28天检测MSCs植入及转分化情况.MSCs移植8周,观察大鼠肺组织病理形态,并进行定量分析;检测凋亡细胞;测定血清和肺组织匀浆中氧化应激水平.结果 MSCs移植后第14、28天,受体肺组织内可见到DAPI标记的MSCs,其中一部分外源性MSCs表达表面活性蛋白C,即一部分植入肺部的MSCs分化成肺泡Ⅱ型上皮细胞.肺气肿组、MSCs移植组肺组织平均内衬间隔均显著高于对照组[(111 ±23)、(90±15)比(74±10)μm,平均肺泡数均显著低于对照组[(94±22)、(125±15)比(159±22)个/mm2](均P＜0.05);肺气肿组肺组织平均内衬间隔显著高于MSCs移植组,而平均肺泡数显著低于MSCs移植组(均P ＜0.05).肺气肿组肺泡壁细胞凋亡指数显著高于MSCs移植组[(13.5±2.5)％比(4.8±0.7)％,P＜0.05].肺气肿组、MSCs移植组血清和肺组织中丙二醇均显著高于对照组[(4.3±0.8)、(3.7±0.4)比(3.0 ±0.4) nmol/ml和(5.4±0.5)、(4.8±0.4)比(4.2±0.6)nmol/mg,均P＜0.05];肺气肿组血清和肺组织中丙二醇均显著高于MSCs移植组(均P＜0.05).肺气肿组、MSCs移植组血清和肺组织中超氧化物歧化酶均显著低于对照组[(8.7±0.8)、(9.6±0.7)比(10.5±0.9) U/ml和(56.3±13.4)、(70.2±11.0)比(84.9±13.0)U/mg,均P＜0.05];肺气肿组血清和肺组织中超氧化物歧化酶均显著低于MSCs移植组(均P＜0.05).结论 骨髓来源MSCs移植可减轻吸烟所致的大鼠肺气肿,其可能机制是MSCs归巢、植入至受损伤的肺组织并分化为肺泡Ⅱ型上皮细胞,MSCs还可能通过抑制细胞凋亡、抑制氧化应激对肺气肿发挥治疗作用.
目的 探討骨髓來源間充質榦細胞(MSCs)移植對大鼠肺氣腫的療效及其可能機製.方法 24隻雌性SD大鼠按隨機數字錶法隨機分為對照組、肺氣腫組、MSCs移植組各8隻,將肺氣腫組與MSCs移植組大鼠煙霧暴露14週,製作肺氣腫大鼠模型,予MSCs移植組大鼠通過尾靜脈輸註6-二乙酰基-2-苯基吲哚(DAPI)標記的骨髓來源MSCs.MSCs移植後第14、28天檢測MSCs植入及轉分化情況.MSCs移植8週,觀察大鼠肺組織病理形態,併進行定量分析;檢測凋亡細胞;測定血清和肺組織勻漿中氧化應激水平.結果 MSCs移植後第14、28天,受體肺組織內可見到DAPI標記的MSCs,其中一部分外源性MSCs錶達錶麵活性蛋白C,即一部分植入肺部的MSCs分化成肺泡Ⅱ型上皮細胞.肺氣腫組、MSCs移植組肺組織平均內襯間隔均顯著高于對照組[(111 ±23)、(90±15)比(74±10)μm,平均肺泡數均顯著低于對照組[(94±22)、(125±15)比(159±22)箇/mm2](均P＜0.05);肺氣腫組肺組織平均內襯間隔顯著高于MSCs移植組,而平均肺泡數顯著低于MSCs移植組(均P ＜0.05).肺氣腫組肺泡壁細胞凋亡指數顯著高于MSCs移植組[(13.5±2.5)％比(4.8±0.7)％,P＜0.05].肺氣腫組、MSCs移植組血清和肺組織中丙二醇均顯著高于對照組[(4.3±0.8)、(3.7±0.4)比(3.0 ±0.4) nmol/ml和(5.4±0.5)、(4.8±0.4)比(4.2±0.6)nmol/mg,均P＜0.05];肺氣腫組血清和肺組織中丙二醇均顯著高于MSCs移植組(均P＜0.05).肺氣腫組、MSCs移植組血清和肺組織中超氧化物歧化酶均顯著低于對照組[(8.7±0.8)、(9.6±0.7)比(10.5±0.9) U/ml和(56.3±13.4)、(70.2±11.0)比(84.9±13.0)U/mg,均P＜0.05];肺氣腫組血清和肺組織中超氧化物歧化酶均顯著低于MSCs移植組(均P＜0.05).結論 骨髓來源MSCs移植可減輕吸煙所緻的大鼠肺氣腫,其可能機製是MSCs歸巢、植入至受損傷的肺組織併分化為肺泡Ⅱ型上皮細胞,MSCs還可能通過抑製細胞凋亡、抑製氧化應激對肺氣腫髮揮治療作用.
목적 탐토골수래원간충질간세포(MSCs)이식대대서폐기종적료효급기가능궤제.방법 24지자성SD대서안수궤수자표법수궤분위대조조、폐기종조、MSCs이식조각8지,장폐기종조여MSCs이식조대서연무폭로14주,제작폐기종대서모형,여MSCs이식조대서통과미정맥수주6-이을선기-2-분기신타(DAPI)표기적골수래원MSCs.MSCs이식후제14、28천검측MSCs식입급전분화정황.MSCs이식8주,관찰대서폐조직병리형태,병진행정량분석;검측조망세포;측정혈청화폐조직균장중양화응격수평.결과 MSCs이식후제14、28천,수체폐조직내가견도DAPI표기적MSCs,기중일부분외원성MSCs표체표면활성단백C,즉일부분식입폐부적MSCs분화성폐포Ⅱ형상피세포.폐기종조、MSCs이식조폐조직평균내츤간격균현저고우대조조[(111 ±23)、(90±15)비(74±10)μm,평균폐포수균현저저우대조조[(94±22)、(125±15)비(159±22)개/mm2](균P＜0.05);폐기종조폐조직평균내츤간격현저고우MSCs이식조,이평균폐포수현저저우MSCs이식조(균P ＜0.05).폐기종조폐포벽세포조망지수현저고우MSCs이식조[(13.5±2.5)％비(4.8±0.7)％,P＜0.05].폐기종조、MSCs이식조혈청화폐조직중병이순균현저고우대조조[(4.3±0.8)、(3.7±0.4)비(3.0 ±0.4) nmol/ml화(5.4±0.5)、(4.8±0.4)비(4.2±0.6)nmol/mg,균P＜0.05];폐기종조혈청화폐조직중병이순균현저고우MSCs이식조(균P＜0.05).폐기종조、MSCs이식조혈청화폐조직중초양화물기화매균현저저우대조조[(8.7±0.8)、(9.6±0.7)비(10.5±0.9) U/ml화(56.3±13.4)、(70.2±11.0)비(84.9±13.0)U/mg,균P＜0.05];폐기종조혈청화폐조직중초양화물기화매균현저저우MSCs이식조(균P＜0.05).결론 골수래원MSCs이식가감경흡연소치적대서폐기종,기가능궤제시MSCs귀소、식입지수손상적폐조직병분화위폐포Ⅱ형상피세포,MSCs환가능통과억제세포조망、억제양화응격대폐기종발휘치료작용.
Objective To explore the effects of transplanting bone marrow mesenehymal stem cells (MSCs) on emphysema in rats and elucidate the possible mechanisms.Methods A total of 24 female Sprague-Dawley rats were randomly divided randomly into 3 groups of control,emphysema and MSCs transplantation (n =8 each).The rat model of emphysema was established by 14-week exposure to cigarette smoking and then MSCs labeled with 4,6-diamidino-2-phenylindole (DAPI) were injected into recipient rats of MSCs transplantation group via tail veins.At 2 and 4 weeks post-transplantation,engraftment and differentiation of MSCs was determined.At 8 weeks post-transplantation,lung fissure sections were prepared for examining the morphological alterations.The apoptosis of alveolar septal cells was assessed.And the levels of oxidative stress in sera and lung were detected.Results At 2 and 4 weeks post-transplantation,MSCs labeled with DAPI could be found in recipient lungs,some of which differentiated into type Ⅱ alveolar epithelial cells.Mean linear intercept was higher in emphysema and MSCs transplantation groups than control group [(111 ±23) and (90 ± 15) vs (74 ± 10) μm],mean alveolar numbers were lower than control group [(94 ± 22) and (125 ± 15) vs (159 ± 22)/mm2] (all P ＜ 0.05);mean linear intercept was higher and mean alveolar numbers were lower in emphysema group than MSCs transplantation group (both P ＜ 0.05).The apoptotic index of alveolar wall cells in emphysema group was higher than MSCs transplantation group [(13.5 ± 2.5) ％ vs (4.8 ± 0.7) ％,P ＜ 0.05].Malondialdehyde of sera and lung in emphysema and MSCs transplantation groups was higher than control group [(4.3 ±0.8),(3.7 ±0.4) vs (3.0 ±0.4) nmol/ml,(5.4 ± 0.5),(4.8 ± 0.4) vs (4.2 ± 0.6) nmol/mg,all P ＜ 0.05];malondialdehyde of sera and lung in emphysema group was higher than MSCs transplantation group (both P ＜ 0.05).Superoxide dismutase (SOD) of sera and lung in emphysema and MSCs transplantation groups was lower than control group [(8.7±0.8),(9.6±0.7) vs (10.5 ±0.9) U/ml and (56.3 ±13.4),(70.2±11.0) vs (84.9± 13.0) U/mg,all P ＜ 0.05];SOD of sera and lung in emphysema group was lower than MSCs transplantation group (both P ＜ 0.05).Conclusion MSCs transplantation via tail vein may arrest the progression of emphysema in a cigarette-smoke-induced rat model of emphysema through a differentiation of injected MSCs into type Ⅱ alveolar epithelial cells and down-regulations of apoptosis and oxidative stress.
